在TRIDENT-2研究中,荷兰的所有孕妇均接受全基因组非侵入性产前检测(GW-NIPT),可选择接受全面筛查或仅接受常见三体筛查.先前的数据表明,GW-NIPT可以可靠地检测普通产科人群中的常见三体,并且该测试还可以检测其他染色体异常(其他发现)。然而,目前缺乏关于筛查其他发现的临床影响的证据.因此,我们提供了TRIDENT-2研究的随访结果,以根据有其他发现的病例的实验室和围产期结局来确定这种临床影响.在2017年4月至2019年4月期间,在402/110,739例怀孕(0.36%)中发现了其他发现。对于358个案例,起源被证明是胎儿(n=79;22.1%),(假设)局限性胎盘镶嵌(CPM)(n=189;52.8%),或母体(n=90;25.1%)。其余44人(10.9%),无法确定像差的起源。大多数胎儿染色体畸变是致病性的,并与严重的临床表型相关(61/79;77.2%)。对于CPM案例,先兆子痫的发生率(8.5%[16/189]对0.5%[754/159,924];RR18.5),与一般产科人群相比,出生体重<2.3百分位数(13.6%[24/177]vs2.5%[3,892/155,491];RR5.5)显著增加。在90个产妇发现中,12例(13.3%)为恶性肿瘤和32例(35.6%)(马赛克)致病性拷贝数变异,主要与轻度或无临床表型有关。这项大型队列研究的数据为决定是否以及如何在筛查计划中实施GW-NIPT提供了重要信息。此外,这些数据可以为具有挑战性的解释提供信息,咨询,以及其他发现的后续行动。
In the TRIDENT-2
study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2
study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight <2.3rd percentile (13.6% [24/177] vs 2.5% [3,892/155,491]; RR 5.5) were significantly increased compared to the general obstetric population. Of the 90 maternal findings, 12 (13.3%) were malignancies and 32 (35.6%) (mosaic) pathogenic copy number variants, mostly associated with mild or no clinical phenotypes. Data from this large cohort
study provide crucial information for deciding if and how to implement GW-NIPT in screening programs. Additionally, these data can inform the challenging interpretation, counseling, and follow-up of additional findings.